Clustering of cancer‐related mutations in a subset of BRCA1 alleles: A study in the Spanish population

Abstract
We have observed that the frequency of D17S855 short alleles (139 bp and 141 bp) in individuals carrying BRCA1 germline mutations is higher than in controls (54% vs. 31%, p = 0.0004). By unambiguously establishing mutation/D17S855 phase in 18 BRCA1‐positive families, we find that most (11 of 15 different mutations) BRCA1 defects are linked to chromosomes with short alleles (OR = 8.21, 95% CI 1.97–39.32, p = 0.0007). We suggest that BRCA1 mutations are not randomly distributed but clustered in a subset of BRCA1 alleles that can be identified by D17S855 genotyping. Further analysis involving a larger set of mutations and different populations are needed to clarify the relevance of this unexpected finding.
Funding Information
  • Aventis, Comunidad de Madrid (08.1/0018.1/2000)
  • Fondo de Investigación Sanitaria (FIS) (01/0024-03, 99/0140)